ArticleAmerican journal of physiology. Heart and circulatory physiology2011
Regulation of in vivo cardiac contractility by phospholemman: role of Na+/Ca2+ exchange.
Article in American journal of physiology. Heart and circulatory physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 37 citations in OpenAlex.
- The functions of FXYD family members in human health and disease.Genes & diseases · 2026Review
- Bag3 Regulates Mitochondrial Function and the Inflammasome Through Canonical and Noncanonical Pathways in the Heart.JACC. Basic to translational science · 2023Article
- Novel BAG3 Variants in African American Patients With Cardiomyopathy: Reduced β-Adrenergic Responsiveness in Excitation-Contraction.Journal of cardiac failure · 2020Article
- Antidotal effects of methylene blue against cyanide neurological toxicity: in vivo and in vitro studies.Annals of the New York Academy of Sciences · 2020Article
- Transient receptor potential ion channel TRPM2 promotes AML proliferation and survival through modulation of mitochondrial function, ROS, and autophagy.Cell death & disease · 2020Article
- Trpm2 enhances physiological bioenergetics and protects against pathological oxidative cardiac injury: Role of Pyk2 phosphorylation.Journal of cellular physiology · 2019Article
- Methylene Blue Counteracts HCardiovascular toxicology · 2018Article
- Haplo-insufficiency of Bcl2-associated athanogene 3 in mice results in progressive left ventricular dysfunction, β-adrenergic insensitivity, and increased apoptosis.Journal of cellular physiology · 2018Article
- Methylene blue counteracts cyanide cardiotoxicity: cellular mechanisms.Journal of applied physiology (Bethesda, Md. : 1985) · 2018Article
- How does pressure overload cause cardiac hypertrophy and dysfunction? High-ouabain affinity cardiac NaAmerican journal of physiology. Heart and circulatory physiology · 2017Review
- Adeno-associated Virus Serotype 9 - Driven Expression of BAG3 Improves Left Ventricular Function in Murine Hearts with Left Ventricular Dysfunction Secondary to a Myocardial Infarction.JACC. Basic to translational science · 2016Article
- Depletion of the Human Ion Channel TRPM2 in Neuroblastoma Demonstrates Its Key Role in Cell Survival through Modulation of Mitochondrial Reactive Oxygen Species and Bioenergetics.The Journal of biological chemistry · 2016Article
- Pivotal role of α2 NaThe Journal of physiology · 2016Review
- β-arrestin-biased signaling through the β2-adrenergic receptor promotes cardiomyocyte contraction.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Methylene blue counteracts H2S toxicity-induced cardiac depression by restoring L-type Ca channel activity.American journal of physiology. Regulatory, integrative and comparative physiology · 2016Article
- BAG3 regulates contractility and Ca(2+) homeostasis in adult mouse ventricular myocytes.Journal of molecular and cellular cardiology · 2016Article
- Cardiac Dysfunction in HIV-1 Transgenic Mouse: Role of Stress and BAG3.Clinical and translational science · 2015Article
- Regulation of L-type calcium channel by phospholemman in cardiac myocytes.Journal of molecular and cellular cardiology · 2015Article
- Ca²⁺ entry via Trpm2 is essential for cardiac myocyte bioenergetics maintenance.American journal of physiology. Heart and circulatory physiology · 2015Article
- Targeting cardiomyocyte Ca2+ homeostasis in heart failure.Current pharmaceutical design · 2015Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Phospholemman (PLM), when phosphorylated at serine 68, relieves its inhibition on Na(+)-K(+)-ATPase but inhibits Na(+)/Ca(2+) exchanger 1 (NCX1) in cardiac myocytes. Under stress when catecholamine levels are high, enhanced Na(+)-K(+)-ATPase activity by phosphorylated PLM attenuates intracellular Na(+) concentration ([Na(+)](i)) overload. To evaluate the effects of PLM on NCX1 on in vivo cardiac contractility, we injected recombinant adeno-associated virus (serotype 9) expressing either the phosphomimetic PLM S68E mutant or green fluorescent protein (GFP) directly into left ventricles (LVs) of PLM-knockout (KO) mice. Five weeks after virus injection, ∼40% of isolated LV myocytes exhibited GFP fluorescence. Expression of S68E mutant was confirmed with PLM antibody. There were no differences in protein levels of α(1)- and α(2)-subunits of Na(+)-K(+)-ATPase, NCX1, and sarco(endo)plasmic reticulum Ca(2+)-ATPase between KO-GFP and KO-S68E LV homogenates. Compared with KO-GFP myocytes, Na(+)/Ca(2+) exchange current was suppressed, but resting [Na(+)](i), Na(+)-K(+)-ATPase current, and action potential amplitudes were similar in KO-S68E myocytes. Resting membrane potential was slightly lower and action potential duration at 90% repolarization (APD(90)) was shortened in KO-S68E myocytes. Isoproterenol (Iso; 1 μM) increased APD(90) in both groups of myocytes. After Iso, [Na(+)](i) increased monotonically in paced (2 Hz) KO-GFP but reached a plateau in KO-S68E myocytes. Both systolic and diastolic [Ca(2+)](i) were higher in Iso-stimulated KO-S68E myocytes paced at 2 Hz. Echocardiography demonstrated similar resting heart rate, ejection fraction, and LV mass between KO-GFP and KO-S68E mice. In vivo closed-chest catheterization demonstrated enhanced contractility in KO-S68E compared with KO-GFP hearts stimulated with Iso. We conclude that under catecholamine stress when [Na(+)](i) is high, PLM minimizes [Na(+)](i) overload by relieving its inhibition of Na(+)-K(+)-ATPase and preserves inotropy by simultaneously inhibiting Na(+)/Ca(2+) exchanger.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.